Neumann, Lisa; Markaki, Yolanda; Mladenov, Emil; Hoffmann, Daniel; Buiting, Karin; Horsthemke, Bernhard:
The imprinted NPAP1/C15orf2 gene in the Prader-Willi syndrome region encodes a nuclear pore complex associated protein
2012
In: Human molecular genetics, Jg. 21 (2012), Heft 18, S. 4038 - 4048
Artikel/Aufsatz in Zeitschrift2012BiologieMedizin
Fakultät für Biologie
Zentrale wissenschaftliche Einrichtungen » Zentrum für Medizinische Biotechnologie (ZMB)
Medizinische Fakultät » Universitätsklinikum Essen » Institut für Humangenetik
Titel:
The imprinted NPAP1/C15orf2 gene in the Prader-Willi syndrome region encodes a nuclear pore complex associated protein
Autor(in):
Neumann, Lisa; Markaki, Yolanda; Mladenov, Emil; Hoffmann, DanielLSF; Buiting, KarinLSF; Horsthemke, BernhardLSF
Erscheinungsjahr
2012
DOI:
WWW URL
Erschienen in:
Titel:
Human molecular genetics
in:
Jg. 21 (2012), Heft 18, S. 4038 - 4048
ISSN:

Abstract:

The Prader-Willi syndrome (PWS) region in 15q11q13 harbours a cluster of imprinted genes expressed from the paternal chromosome only. Whereas loss of function of the SNORD116 genes appears to be responsible for the major features of PWS, the role of the other genes is less clear. One of these genes is C15orf2, which has no orthologues in rodents, but appears to be under strong positive selection in primates. C15orf2 encodes a 1156 amino acid protein with six nuclear localisation sequences. By protein BLAST analysis and InterProScan signature recognition search, we found sequence similarity of C15orf2 to the nuclear pore complex (NPC) protein POM121. To determine whether C15orf2 is located at nuclear pores, we generated a stable cell line that inducibly expresses FLAG-tagged C15orf2 and performed immunocytochemical studies. We found that C15orf2 is present at the nuclear periphery, where it colocalizes with NPCs and nuclear lamins. At very high expression levels, we observed invaginations of the nuclear envelope. Extending these observations to three-dimensional structured illumination microscopy, which achieves an 8-fold improved volumetric resolution over conventional imaging, we saw that C15orf2 is located at the inner face of the nuclear envelope where it strongly associates with the NPC. In nuclear envelope isolation and fractionation experiments, we detected C15orf2 in the NPC and lamina fractions. These experiments for the first time demonstrate that C15orf2 is part of the NPC or its associated molecular networks. Based on our findings, we propose 'Nuclear pore associated protein 1' as the new name for C15orf2.